PB2333: CAR-T CELL THERAPY IS A EXCELLENT STRATEGY FOR R/R B-NHL
Authors: Liu Rui, Fan Yang, Fei Xue, Hui Shi, Peihao Zheng, Lixia MA, Shaomei Feng, Yuelu Guo, Teng Xu, Zhonghua Fu, Biping Deng, Xiaoyan Ke, Kai Hu
Journal: HemaSphere (2023)

Topic: 19. Aggressive Non-Hodgkin lymphoma - Clinical Background: Chimeric antigen receptor (CAR) T-cell therapy has demonstrated efficacy in treating relapsed/refractory B-cell non-Hodgkin lymphoma (R/R B-NHL). However, some patients experience relapse due to a high tumor burden prior to CAR T-cell therapy, which poses a significant challenge for disease control. Moreover, patients who have achieved complete remission through salvage chemotherapy often fail to meet the inclusion criteria for clinical trials of CAR-T therapy, as well as the indications for commercial CAR-T therapy.Currently, there are very few clinical trials investigating consolidation with CAR T-cell therapy for patients with R/R B-NHL in complete remission (CR). Aims: This study aims to assess the safety and long-term effectiveness of CAR-T therapy as consolidation therapy for R/R B-NHL patients who achieve CR after salvage therapy. Methods: From June 2019 to June 2022,36 patients with relapsed/refractory B-NHL who has achieved complete remission after salvage chemotherapy were included in the study.Patients diagnosed with BL,HGBL,PCNSL,PMBL were combined with autologous stem cell transplantation(ASCT).Diagnoses included DLBCL NOS(n=18),PCNSL(n=6),HGBL(n=2),BL(n=2),Richter(n=1),FL(n=1),PMBCL(n=4) and SCNSL(n=2).Median age was 51 years (range 21-76).75% (27/36) received ≧3 lines of prior treatment.19% (7/36) patients had experienced failure of prior ASCT.52% (12/23) cases were found to have TP53 mutations. Results: After a median follow-up of 15.32 months(range 4.9-43.4), 91.67% (33/36) of patients continuing to have a complete response and 97% (35/36) survival. One-year progression free survival and overall survival were 89% and 95%, respectively.15 patients received CAR T-cells infusion alone and 21 patients received CAR T-cells combined with ASCT.The median dose of CAR-T cell infusion was 1.9 x 10^6/kg and it rapidly expanded after infusion in 33 patients.Median peak expansion occured on day 11 which is 3.365*10^7/L(PB) as measured by Flow Cytometry and 5032 copy/reaction system by quantitative PCR.69.4% (24/36) experienced cytokine release syndrome(CRS) and 5.6%(2/36)was ≥grade 3 CRS and no neurological events. Steroids were used by 22.2% (8/36) of patients at a median dose of 18 mg, and 2.7% (1/36) required tocilizumab for CRS management. 27.8%(10/36) experienced pulmonary infections and intestinal infections were observed in 19.4%(7/36).The group that received CAR-T therapy combined with ASCT achieved neutrophil and platelet engraftment in all cases on median days 12 (range 8-33) and 13 (range 5-63), respectively. Summary/Conclusion: CAR-T combined with or without ASCT as the consolidation therapy is safe for patients with agressive R/R B-NHL who has achieved complete remission after salvage chemotherapy.This approach significantly reduces the relapse rate and mortality, and prolongs progression-free survival. Combining CAR-T therapy with ASCT does not increase the risk of cytokine release syndrome or infection. Furthermore, CAR-T cell expansion does not appear to be affected by tumor burden.Nonetheless, larger patient cohorts and longer follow-up periods are necessary to fully evaluate the clinical application of this approach in the future.Keywords: Autologous hematopoietic stem cell transplantation, Consolidation, CAR-T